The oral mucosa is situated in the front line of defense against potential infections and the tonsils are secondary lymphoid organs that play a crucial role in initiating immune responses against bacterial and viral antigens. It is well established that the central nervous system can modulate several aspects of immune function. Reciprocally, products of immune cells can signal the brain and thereby coordinate a series of systemic and behavioral responses collectively known as the acute-phase response. During infection, proinflammatory cytokines released from antigen-activated immune cells, play a key role as regulators of the host defense response by providing bi-directional signals between the immune and the central nervous systems. The participation of neural afferents in the transmission of peripheral immune signals to the brain has been hypothesized and we have shown that glossopharyngeal afferents are the neural pathways by which immune challenge of the posterior oral cavity conveys information to the brain and elicits central nervous system manifestations of the acute-phase response. However, the anatomical characterization of the glossopharyngeal neuroimmune connection with lymphoid tissues in the oral cavity of the rat remains to be elucidated. Our overall hypothesis states that the glossopharyngeal nerve mediates the immune functions of the nasopharyngeal and palatine lymphoid tissues of the rat. The first corollary hypothesis states that glossopharyngeal innervation provides the neuroanatomical substrate for the neuroimmune connections of the nasopharyngeal lymphoid tissues. The second corollary hypothesis states that the glossopharyngeal nerves convey the response of nasopharyngeal and palatine lymphoid tissues to local immune challenge. The third corollary hypothesis states that the local immune response of nasopharyngeal and palatine lymphoid tissues is regulated by the glossopharyngeal nerves. Specifically, we aim to: 1) characterize the neuroanatomical connections of the glossopharyngeal nerves with the nasopharyngeal lymphoid tissues; 2) determine the response of the glossopharyngeal nerve to immune challenge of the soft palate; and 3) investigate the role of the glossopharyngeal nerve in regulating the local immune response of the nasopharyngeal and palatine lymphoid tissues. Neuroimmune characterization of this pathway should provide insight into the pathophysiology of the oral cavity related to local inflammatory diseases, including oral cancer and mucosal diseases.